The incidence of diabetes is increasing rapidly as a result of the obesity epidemic. The Mouse Phenotyping, Physiology and Metabolism Core supports the overall mission of the Penn DRC to prevent, treat, and cure diabetes mellitus. Our understanding of the pathogenesis of diabetes, obesity and other metabolic disorders has benefited from the use of gene targeting methodology in mice to elucidate molecular mechanisms. However, such efforts are often hampered by a lack of facilities or expertise for metabolic phenotyping. The Mouse Phenotyping, Physiology and Metabolism Core provides investigators of the Penn Diabetes Research Center (DRC) with state-of-the-art, timely and cost-effective diagnostic studies in mice. The core offers consultation and experimental design, monitoring of feeding, drinking, energy expenditure, locomotor activity and sleep epochs using a Comprehensive Laboratory Animal Monitoring System (CLAMS), measurement of body composition using dual emission x-ray absorptiometry (DEXA) or nuclear magnetic resonance spectroscopy, and assessment of glucose homeostasis with glucose and insulin tolerance tests, and insulin clamp and radioactive tracer kinetics. Studies in the core are performed by two research specialists under the direction of Rexford Ahima. The core maintains a database of metabolic and hormonal parameters in mouse models of diabetes and obesity, and coordinates its services with other core laboratories, i.e. Islet Biology (Franz Matschinsky; Doris Stoffers), Radioimmunoassay and Biomarkers (Muredach Reilly), Transgenic and Chimeric (Nancy Cooke; Stephen Liebhaber), and Functional Genomics Core (Klaus Kaestner). These efforts facilitate in vivo metabolic phenotyping of mice, and the translation of ideas from the bench to mice, and ultimately to humans.